Occult gallbladder carcinoma after laparoscopic cholecystectomy: a report of four cases.

Eighty-four patients underwent laparoscopic cholecystectomy (LC) from January through August 2006. Of these patients, 4 (4.7%) were found to have occult gallbladder carcinoma (GC) either during or after the procedure. Two of the patients were women and 2 were men. The mean age was 75.0 years. One patient had mucosal tumors, 2 had subserosal tumors, and 1 had a serosal lesion. One of the 2 patients with subserosal tumors underwent radical surgery. In a previous study, 0.83% (10 of 1,195) of patients who had undergone LC were found to have occult GC, either during of after the procedure. The prevalence of gallbladder carcinoma has recently been increasing. GC has been reported in 0.3% to 1.5% of patients who have undergone cholecystectomy. Since the introduction of laparoscopic surgery, the number of cholecystectomies being performed has increased, which may explain why occult GC seems to be occurring more frequently. The prognosis for GC is poor, and surgical resection is the only potentially curative treatment. However, GC is difficult to diagnose at an early stage and difficult to recognize even in the advanced stages. Fifteen percent to 30% of patients show no preoperative or intraoperative evidence of malignancy. Occult GC is also increasing. Because flat infiltrating GC and GC with cholecystitis and numerous stones are difficult to diagnose preoperatively, we recommend taking frozen sections from patients who are of advanced age (older than 70 years), have a long history of stones, or have a thickened gallbladder wall.     

Changes in Lymphangiogenesis and Vascular Endothelial Growth Factor Expression by Neo‐Adjuvant Hormonal Therapy in Prostate Cancer Patients

BACKGROUND

The anti‐cancer mechanism of neo‐adjuvant hormonal therapy (NHT) is not well understood. Lymphangiogenesis plays an important role in cancer progression and is regulated by a complex mechanism that includes vascular endothelial growth factor (VEGF) signaling. However, there is little information regarding relationship between lymphangiogenesis and androgen deprivation. The aim of this study was to clarify changes in lymphangiogenesis and VEGF expression induced by androgen deprivation in prostate cancer in vivo and in vitro.

METHODS

Patients who had undergone a radical prostatectomy were enrolled in the study (NHT, n = 60 and non‐NHT, n = 64). Lymph vessels were identified by D2‐40 immunoreactivity and lymph vessel density and lymph vessel area (LVD and LVA, respectively) were measured from micrographs. The expression of VEGF‐A, ‐B, ‐C, and ‐D was evaluated by immunohistochemistry. The prognostic value of LVD and LVA for biochemical recurrence was also investigated.

RESULTS

Mean LVD ± SD was higher in the NHT than in the non‐NHT group (11.3 ± 3.0 vs. 7.1 ± 3.4 per high power field; P < 0.001). LVA was larger in the NHT than in the non‐NHT group (512.8 ± 174.9 vs. 202.7 ± 72.8 µm²; P < 0.001). VEGF‐A expression was lower whereas VEGF‐C and ‐D levels were higher in the NHT than in the non‐NHT group. VEGF‐B expression in specimens with NHT was lower than that in biopsy specimens at diagnosis. These results were confirmed by in vitro studies used androgen‐sensitive prostate cancer cell line. LVA was found to be an independent predictor of biochemical recurrence in patients who received NHT.

CONCLUSIONS

Our results demonstrate that NHT stimulates lymphangiogenesis via upregulation of VEGF‐C and ‐D, which may increase LVA and affect the outcome of prostate cancer patients. This findings were supported by in vitro data of prostate cancer cell. Prostate 77:255–262, 2017. © 2016 The Authors. The Prostate Published by Wiley Periodicals, Inc.     

Optical Dynamic Analysis of Thrombus Inside a Centrifugal Blood Pump During Extracorporeal Mechanical Circulatory Support in a Porcine Model

Complications due to pump thrombus remain the weak point of mechanical circulatory support (MCS), such as the use of a left ventricular assist device (LVAD) or extracorporeal membrane oxygenation, leading to poor outcomes. Hyperspectral imaging (HSI) is an effective imaging method using a hyperspectral (HS) camera, which comprises a spectrophotometer and a charge‐coupled device camera to discriminate thrombus from whole blood. Animal experiments were conducted to analyze dynamic imaging of thrombus inside a prototype of a hydrodynamically levitated centrifugal blood pump using an HSI system. Six pigs were divided into a venous circulation group (n = 3) and an arterial circulation group (n = 3). Inflow and outflow cannulae were inserted into the jugular veins in the venous circulation group. The latter simulated an LVAD application. To create thrombogenic conditions, pump flow was maintained at 1 L/min without anticoagulation. An image of the bottom surface of the pump was captured by the HS camera every 4 nm over the wavelength range of 608–752 nm. Real‐time dynamic images of the inside of the pump were displayed on the monitor. Appearance of an area displaying thrombus was detected within 24 h after the start of the circulation in every experiment. This imaging system also succeeded in determining the origins of pump thrombus: from inside the pump in two cases, and from outside in four cases. Two main possible sources of pump thrombus originating outside the pump were identified on autopsy: wedge thrombus around the inflow cannula; and string‐like thrombus at the junction between the pump inlet and circuit tube. The results of this study from close observation of the changing appearance of pump thrombus may contribute to improvements in the safety of extracorporeal MCS.     

Regulation of MEK inhibitor selumetinib sensitivity by AKT phosphorylation in the novel BRAF L525R mutant

Background

Oncogenic mutations in BRAF genes are found in approximately 5–10% of colorectal cancers. The majority of BRAF mutations are located within exons 11–15 of the catalytic kinase domains, with BRAF V600E accounting for more than 80% of the observed BRAF mutations. Sensitivity to BRAF- and mitogen-activated protein kinase (MEK) inhibitors varies depending on BRAF mutations and tumor cell types. Previously, we newly identified, BRAF L525R-mutation, in the activation segment of the kinase in colorectal cancer patient. Here, we characterized the function of the BRAF L525R mutation.

Methods

HEK293 cells harboring a BRAF mutation (V600E or L525R) were first characterized and then treated with cetuximab, dabrafenib, and selumetinib. Cell viability was measured using WST-1 assay and the expression of proteins involved in the extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) signaling pathways was evaluated using western blot analysis.

Results

The MEK inhibitor selumetinib effectively inhibited cell proliferation and ERK phosphorylation in BRAF L525R cells but not in BRAF V600E cells. Further studies revealed that AKT phosphorylation was reduced by selumetinib in BRAF L525R cells but not in BRAF V600E cells or selumetinib-resistant BRAF L525R cells. Moreover, the AKT inhibitor overcame the selumetinib resistance.

Conclusions

We established a model system harboring BRAF L525R using HEK293 cells. BRAF L525R constitutively activated ERK. AKT phosphorylation caused sensitivity and resistance to selumetinib. Our results suggest that a comprehensive network analysis may provide insights to identify effective therapies.

     

Choroidal neovascularization imaging using multiple en face optical coherence tomography angiography image averaging

Graefe's Archive for Clinical and Experimental Ophthalmology - To determine the effects of averaging five en face optical coherence tomography angiographic (OCTA) images on the quality of the...     

Presence of Modic type 1 change increases risk of postoperative pyogenic discitis following decompression surgery for lumbar canal stenosis

Study Design

Multicenter retrospective study.

Ratio of C-reactive protein to albumin is a prognostic factor for operable non-small-cell lung cancer in elderly patients

Purpose

The aim of this retrospective study was to evaluate inflammation-based scoring as a prognostic factor for operable non-small-cell lung cancer (NSCLC) in elderly patients.

Methods

We collected preoperative data from 108 patients aged above 80 years with NSCLC. Inflammation-based scoring systems, including the C-reactive protein to albumin ratio (CAR) and the Glasgow prognostic score (GPS), as well as other clinicopathological factors, were evaluated as potential prognostic factors.

Results

The median patient age was 82 (range 80–93) years and the 5-year overall and disease-specific survival rates were 49.7 and 73.9%, respectively. The cut-off value for CAR was calculated using a receiver operator characteristics analysis and patients were dichotomized accordingly. Patients with a low CAR had significantly higher overall survival than those with a high CAR (<0.028; 65.2% vs. ≥0.028; 31.0%, respectively; p < 0.01). In univariate analysis, female gender, a low Charlson comorbidity index of 0 or 1 and a low CAR were significantly identified in overall survival. On multivariate analysis, a low CAR (p = 0.03, hazard ratio: 2.13, 95% confidence interval 1.074–4.295) was identified as a significant prognostic factor.

Conclusions

The preoperative CAR is a useful predictor of overall survival and could be a simple prognostic tool to help identify resectable NSCLC in elderly patients.

     

Outcomes of lung cancer surgery in patients with coronary artery disease: a decade of experience at a single institution

Purpose

The aim of this study is to investigate the surgical outcomes of surgery for non-small cell lung cancer (NSCLC) in patients with coronary artery disease (CAD).

Methods

Among 805 patients who underwent surgery for NSCLC at our hospital within a recent 10-year period, 43 (5.3 %) had a history of CAD. We analyzed the surgical outcomes and risk factors for postoperative complications in these 43 patients.

Results

The postoperative mortality and morbidity rates were 2 and 42 %, respectively. The morbidity rate was significantly higher in the patients with CAD than in those without CAD (P < 0.01). Postoperative cerebrovascular or cardiovascular events occurred in four patients (9 %). Having two of the following was significantly associated with the development of postoperative complications: decreased cardiac function, respiratory dysfunction, or deteriorated renal function (p = 0.04). The 5-year overall and disease-free survival rates of the patients with CAD were 75.6 and 64.5 %, respectively; comparable with those of the patients without CAD; at 77.9 % and 72.5 %, respectively (p = 0.46 and 0.69).

Conclusions

Patients with NSCLC and a history of CAD are at higher risk of complications after pulmonary resection. Combined decreased organ function is a risk factor for postoperative complications. CAD did not influence the long-term outcomes of patients after pulmonary resection for NSCLC.